Variant 11-102714626-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002424.3(MMP8):c.1120G>A(p.Val374Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,540,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

MMP8
NM_002424.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.547

Variant links:

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MMP8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035156935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3 linkuse as main transcript	c.1120G>A	p.Val374Ile	missense_variant	8/10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MMP8	ENST00000236826.8 linkuse as main transcript	c.1120G>A	p.Val374Ile	missense_variant	8/10	1	NM_002424.3	ENSP00000236826	P1
MMP8	ENST00000438475.2 linkuse as main transcript	c.962+678G>A		intron_variant		5		ENSP00000401004
MMP8	ENST00000528662.6 linkuse as main transcript	c.*1097G>A		3_prime_UTR_variant, NMD_transcript_variant	10/12	5		ENSP00000431431

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151666

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.0000947

AC:

AN:

200660

Hom.:

AF XY:

0.0000638

AC XY:

AN XY:

109770

show subpopulations

Gnomad AFR exome

AF:

0.000411

Gnomad AMR exome

AF:

0.0000853

Gnomad ASJ exome

AF:

0.000113

Gnomad EAS exome

AF:

0.0000842

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000972

AC:

135

AN:

1388728

Hom.:

Cov.:

AF XY:

0.000104

AC XY:

AN XY:

689768

show subpopulations

Gnomad4 AFR exome

AF:

0.000306

Gnomad4 AMR exome

AF:

0.0000599

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000296

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.0000525

GnomAD4 genome

AF:

0.000158

AC:

AN:

151780

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.0000840

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000989

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.1120G>A (p.V374I) alteration is located in exon 8 (coding exon 8) of the MMP8 gene. This alteration results from a G to A substitution at nucleotide position 1120, causing the valine (V) at amino acid position 374 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.77

M_CAP

Benign

0.0040

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.92

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.65

REVEL

Benign

0.023

Sift

Benign

0.096

Sift4G

Benign

0.085

Polyphen

0.24

Vest4

0.12

MVP

0.38

MPC

0.037

ClinPred

0.015

GERP RS

2.7

Varity_R

0.046

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over